Heart failure is associated with the activation of compensatory mechanisms which tend to restore cardiac output and maintain tissue perfusion. These mechanisms appear to differ early and late in the evolution of heart disease and to vary depending on the etiology of the heart disease. Some of the factors which contribute to compensatory adjustments or result from the primary cardiac disorder have the potential to influence the regulation of vasopressin secretion from the neurohypophysis. Little is known about the regulation of vasopressin in heart disease. Despite the expectation that vasopressin should increase and contribute to retention of fluids, this remains unsettled. These considerations are the basis of this proposal, which is directed at questions in four areas. 1) Is ADH activity increased in the different phases of heart failure? Is there any impairment of the inhibitory influence on ADH release by arterial baroreceptors and cardiopulmonary receptors with vagal afferents? Does the reflex inhibition of ADH release vary in different types of heart failure? 2) Is heart failure associated with enhanced activation of brain ventricular receptors mediating ADH secretion from the neurohypophysis? 3) Is heart failure associated with an alteration in the sensitivity (number or affinity) of brain ventricular receptors, which mediate ADH release? 4) Does treatment with digoxin or diuretics result in increases or decreases in plasma ADH in heart failure? Can the effect of diuretics be reproduced by inducing hypokalemia with a potassium deficient diet? Can the effect of digoxin be reproduced by the brain ventricular administration of digoxin?